Pharmacokinetics and pharmacodynamics of mitragynine, the principle alkaloid of Mitragyna speciosa: present knowledge and future directions in perspective of pain.

Mitragyna speciosa, commonly known as Ketum or Biak in Malaysia and Kratom in Thailand, is a native plant to Southeast Asia and has various pharmacological benefits. Mitragynine (MG) is the principal alkaloid found in the leaves of Mitragyna speciosa and has been reported to be responsible for the plant's therapeutic actions. Traditionally, local communities use Kratom preparations for relief from different types of pain. The potential analgesic effects of MG using rodent models have been reported in literatures. We have reviewed the published analgesic and pharmacokinetic studies and all of these findings showed the routes of drug administration, doses employed, and type of vehicles used to solubilize the drug, varied considerably; hence this posted difficulties in predicting the drug's pharmacokinetic-response relationship. A rational approach is warranted for accurate prediction of dose-response relationship; as this is essential for the development of MG as an alternative medicinal drug for pain management. PKPD modeling would serve as a better method to understand the dose-response relationship in future MG preclinical and clinical studies.